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Establishing Consensus Understanding of the Barriers to Drug Development in Lupus

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Abstract

Objective

Due to the extreme heterogeneity of lupus and the lack of consensus among stakeholders, pharmaceutical and biotechnology companies have had limited success in developing treatments for lupus. For this reason, the Lupus Foundation of America (LFA), researchers at the Center for the Study of Drug Development at Tufts University School of Medicine (Tufts CSDD) and an advisory committee of 13 international lupus experts collaborated to launch the Addressing Lupus Pillars for Health Advancement (ALPHA) project.

Methods

To inform the ALPHA project, 17 in-depth interviews among lupus experts and a global survey among lupus drug development and clinical care professionals was conducted to identify, characterize, and prioritize fundamental barriers and validate findings.

Results

The global survey received 127 responses from experts across 20 countries. Results of the in-depth interviews and the survey findings were consistent. Top barriers to developing new medical treatments for lupus included the lack of a clear definition of the disease with respondents identifying 30 autoimmune conditions that may be lupus-related; lack of predictive biomarkers; flaws in clinical trial designs; and a lack of reliable outcome measures.

Conclusion

The study findings encourage drug development professionals to validate disease-specific measures and to identify if specific symptoms are caused by lupus. This original research also provides a methodology that can be applied to highly heterogenous diseases where low consensus on diagnosis and treatment exists among drug development and health professionals.

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References

  1. Anjorin A, Lipsky P. Engaging African ancestry participants in SLE clinical trials. Lupus Sci Med. 2018;5(1):e000297. https://doi.org/10.1136/lupus-2018-000297.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Merrill JT, Manzi S, Aranow C, et al. Lupus community panel proposals for optimising clinical trials. Lupus Sci Med. 2018;5(1):e000258corr1. https://doi.org/10.1136/lupus-2018-000258.

    Article  Google Scholar 

  3. Stojan G, Petri M. Epidemiology of systemic lupus erythematosus: an update. Curr Opin Rheumatol. 2018;30(2):144–50. https://doi.org/10.1097/BOR.0000000000000480.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lim SS, Kan H, Pobiner BF, Bao G, Drenkard C. Patient perceptions and preferences of biologic therapies in SLE. Lupus Sci Med. 2019;6:e000322. https://doi.org/10.1136/lupus-2019-000322.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Weldring T, Smith SM. Patient-Reported Outcomes (PROs) and Patient-Reported Outcome Measures (PROMs). Health Serv Insights. 2013;6:61–8. https://doi.org/10.4137/HSI.S11093.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Dall’Era M, Cisternas MG, Snipes K, Herrinton LJ, Gordon C, Helmick CG. The incidence and prevalence of systemic lupus erythematosus in San Francisco County, California: the California Lupus Surveillance Project. Arthritis Rheumatol. 2017;69(10):1996–2005. https://doi.org/10.1002/art.40191.

    Article  PubMed  Google Scholar 

  7. The U.S. Food and Drug Administration: FDA approves first treatment for pediatric patients with lupus. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-pediatric-patients-lupus (2019). Accessed 17 Dec 2019

  8. PhRMA: PhRMA and lupus foundation of america report more than 300 medicines in development for autoimmune diseases. https://www.phrma.org/en/Press-Release/phrma-and-lupus-foundation-of-america-report-more-than-300-medicines-in-development-for-autoimmune-diseases (2016). Accessed 17 Dec 2019

  9. Hay M, Thomas D, Craighead J, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014;32:40–51. https://doi.org/10.1038/nbt.2786.

    Article  CAS  PubMed  Google Scholar 

  10. Furie RA, Morand EF, Bruce IN. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol. 2019;1:e208–19. https://doi.org/10.1016/S2665-9913(19)30076-1.

    Article  Google Scholar 

  11. Dolgin E. Lupus in crisis: as failures pile up, clinicians call for new tools. Nat Biotechnol. 2019;37:7–8. https://doi.org/10.1038/nbt0119-7.

    Article  CAS  PubMed  Google Scholar 

  12. Manzi S, Raymond S, Tse K, et al. Global consensus building and prioritisation of fundamental lupus challenges: the ALPHA project. Lupus Sci Med. 2019;6(1):e000342. https://doi.org/10.1136/lupus-2019-000342.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Qi S, Chen Q, Xu D, Xie N, Dai Y. Clinical application of protein biomarkers in lupus erythematosus and lupus nephritis. Lupus. 2018;27(10):1582–90. https://doi.org/10.1177/0961203318773643.

    Article  CAS  PubMed  Google Scholar 

  14. Felten R, Sagez F, Gavand PE, et al. 10 most important contemporary challenges in the management of SLE. Lupus Sci Med. 2019;6(1):e000303. https://doi.org/10.1136/lupus-2018-000303.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Idborg H, Zandian A, Sandberg AS, et al. Two subgroups in systemic lupus erythematosus with features of antiphospholipid or Sjögren’s syndrome differ in molecular signatures and treatment perspectives. Arthritis Res Ther. 2019;21(1):62. https://doi.org/10.1186/s13075-019-1836-8.

    Article  PubMed  PubMed Central  Google Scholar 

  16. van Vollenhoven RF, Petri MA, Cervera R, et al. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis. 2012;71(8):1343–9. https://doi.org/10.1136/annrheumdis-2011-200937.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Furie R, Khamashta M, Merrill JT, et al. Anifrolumab, an anti-interferon-α receptor monoclonal antibody, in moderate-to-severe systemic lupus erythematosus. Arthritis Rheumatol. 2017;69(2):376–86. https://doi.org/10.1002/art.39962.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Liu CC, Kao AH, Manzi S, Ahearn JM. Biomarkers in systemic lupus erythematosus: challenges and prospects for the future. Ther Adv Musculoskelet Dis. 2013;5(4):210–33. https://doi.org/10.1177/1759720X13485503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Merrill JT, Immermann F, Whitley M, et al. The biomarkers of lupus disease study: a bold approach may mitigate interference of background immunosuppressants in clinical trials. Arthritis Rheumatol. 2017;69(6):1257–66. https://doi.org/10.1002/art.40086.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. OMERACT Home: OMERACT. https://omeract.org/. Accessed 30 Jan 2020

  21. Doamekpor LA, Zuckerman DM. Lack of diversity in cancer drug clinical trials may exacerbate racial disparities in mortality rates. Cancer Epidemiol. 2014;38(5):645–6. https://doi.org/10.1016/j.canep.2014.06.007.

    Article  PubMed  Google Scholar 

  22. Lupus Foundation of America. https://www.lupus.org/news/lupus-foundation-of-america-survey-more-than-half-of-americans-lack-awareness-understanding-of-lupus# (2019). Accessed 17 Dec 2019

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Acknowledgements

Authors would like to thank all of the individuals who participated in the expert interviews and in the global survey and members of the Global Advisory Committee (GAC).

Funding

The ALPHA Project was launched in partnership with founding partner EMD Serono Research & Development, Inc. (a business of Merck KGaA, Darmstadt, Germany) and through additional support by GlaxoSmithKline. These organizations providing a grant to support this research study.

Author information

Authors and Affiliations

  1. Tufts Center for the Study of Drug Development, Tufts University School of Medicine, Boston, MA, 02111, USA

    Yaritza Peña BS & Kenneth Getz MBA

  2. Lupus Foundation of America, Washington, DC, 20037, USA

    Karin Tse MPH & Leslie M. Hanrahan BS

  3. Center for Information and Study on Clinical Research Participation, Boston, MA, 02109, USA

    Annick de Bruin MBA

  4. Monash University, Clayton, Melbourne, 3168, Australia

    Eric F. Morand MB, BS, PhD

Authors
  1. Yaritza Peña BS
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  2. Karin Tse MPH
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  3. Leslie M. Hanrahan BS
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  4. Annick de Bruin MBA
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  5. Eric F. Morand MB, BS, PhD
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  6. Kenneth Getz MBA
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Contributions

All authors contributed to the discussions and data interpretation contained in this paper and provided input on the manuscript and approved its final version. YP and AA conducted expert interviews, survey programming, and data analysis. YP contributed to manuscript writing, EFM and KT contributed to finalizing. KG and LMH oversaw and approved all research efforts.

Corresponding author

Correspondence to Yaritza Peña BS.

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Conflict of interest

Dr. Morand reports grants and personal fees from AstraZeneca, grants and personal fees from Bristol Myers Squibb, grants and personal fees from Janssen, personal fees from AbbVie, grants and personal fees from Eli Lilly, non-financial support from Roche, personal fees from Biogen, personal fees from Neovacs, personal fees from Wolf Bio, outside the submitted work; Dr. Getz reports grants from Lupus Foundation of America, during the conduct of the study.

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Peña, Y., Tse, K., Hanrahan, L.M. et al. Establishing Consensus Understanding of the Barriers to Drug Development in Lupus. Ther Innov Regul Sci 54, 1159–1165 (2020). https://doi.org/10.1007/s43441-020-00134-2

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  • DOI: https://doi.org/10.1007/s43441-020-00134-2

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